Effects of methoprene and juvenile hormone on larval ecdysis,emergence, and metamorphosis of the endoparasitic wasp, Apanteles congregatus

Topical application of juvenile hormone I and III or the hormone analogue methoprene to parasitized Manduca sexta larvae inhibited subsequent emergence of the endoparasitic wasp Apanteles congregatus. Methoprene treatment inhibited wasp emergence in a dose-dependent manner, causing either a delay or total inhibition of emergence. These results were interpreted as reflecting inhibitory effects of juvenile hormone on the second-larval ecdysis of the parasitoid that normally occurs during emergence from the host larva. Parasitoid ecdysis was disrupted even when methoprene was applied to host larvae a few hours prior to the normal expected time of emergence. A correlation between the number of emerging parasitoids and the timing of emergence was seen in methoprene-treated hosts, and few parasitoids emerged after day 9 of the host's fifth-instar. Our findings suggest that the suppression of emergence by juvenile hormone analogues noted in previous studies may be due to a similar inhibitory effect on parasitoid ecdysis. We also observed that parasitoids emerging from hosts treated with a low dose of methoprene (1 μg) later pupated normally but then formed nonviable pupal-adult intermediates. Thus use of this insect growth regulator must be undertaken carefully to prevent possible adverse effects on natural parasitoid populations.     

In vivo stimulation of vitellogenesis in Aedes aegypti with juvenile hormone,juvenile hormone analogue (ZR 515) and 20-hydroxyecdysone

Decapitated blood-fed Aedes aegypti mosquitoes do not undergo normal oöcyte maturation. Topical application of 1.25 ng JH analogue (ZR 515) or 250 ng JH-I restored ovarian development in 70–80% of the treated females. The rate of vitellogenin synthesis in these animals was 80% of normal blood-fed controls.When ligated abdomens were treated, 125 pg ZR 515 or 12.5 ng JH-I were sufficient to restore ovarian development in 80% of the animals. The rate of vitellogenin synthesis in these animals was 70% of normal blood-fed controls. On the other hand, injection of 1.25 μg 20-hydroxyecdysone was needed to restore ovarian development and vitellogenin synthesis in decapitated and abdominally ligated females.These experiments indicate that JH concentrations closer to the physiological norm than 20-hydroxyecdysone, can restore ovarian development and vitellogenin synthesis in vivo.     

The onset of metamorphosis in Tenebrio molitor L.: Effects of a juvenile hormone analogue and of 20-hydroxyecdysone

Sensitivity to juvenile hormone and to 20-hydroxyecdysone has been investigated during the last-larval stages of Tenebrio molitor. Topical applications of a juvenile hormone analogue (K-421d) showed that the sensitive period, occurring before apolysis, is relatively short (less than 4 days in a 3-week instar) and divided into two phases. Treatment during the first and longest phase induced a delay in development and then an increase in larval moult percentage. Treatment during the second phase induced several abnormal moults (prothetelic larvae and larval-pupal intermediates).Injections of massive doses of 20-hydroxyecdysone (10 μg per animal) also evidenced a period of disturbance of the morphogenetic programme, beginning before pupal apolysis but continuing several days after.Comparison of the sensitive periods to both hormones suggests that a very important and rapid step of the larval-pupal programme change is controlled hormonally just before pupal apolysis.     

Effects of a juvenile hormone analogue on the duration of the fifth instar in the milkweed bug Oncopeltus fasciatus

Topical application of JHA to fifth instar nymphs of Oncopeltus fasciatus, immediately following ecdysis from the fourth instar, decreases the duration of the fifth instar by approximately 36 hr in addition to inducing a supernumerary larval moult. JHA appears to accelerate the time of subsequent ecdysis in two ways: first, the onset of ecdysone secretion is accelerated, and is accompanied by a similarly premature initiation of mitotic activity in epidermal cells. This is the classical prothoracicotropic action of JH. Second, the period between the onset of mitotic activity and the time of ecdysis itself is shortened. That is, once cellular activities associated with the moulting cycle are triggered by ecdysone, such activities are completed more rapidly in the presence of JHA. It appears that the larval-larval moult induced by JHA requires intrinsically less time to accomplish than a normal metamorphic moult.     

The effects of mating,exogenous juvenile hormone and a juvenile hormone analogue on pheromone titre,calling and oviposition in the omnivorous leafroller moth (Platynota stultana)

Mating in Platynota stultana resulted in the termination of calling, the gradual reduction of pheromone in the pheromone glands to non-detectable levels (<0.1 ng/♀) within 14 h, and oviposition of the first batch of eggs 20–24 h after copulation. Decapitation of virgin females resulted in a similar decline in pheromone titre, and also eliminated oviposition and calling. Pheromone production appears to be controlled via the head. Mating probably terminates neural or hormonal input required for pheromone production and/or removes neural or hormonal inhibition of pheromone degradation. A juvenile hormone analogue (ZR-512) and juvenile hormones I, II and III applied exogenously to virgin females elicited oviposition comparable to mated females and terminated calling within 48 h. The juvenile hormone analogue also appeared to block pheromone production in virgin females. These results suggest that juvenile hormone may be involved in the switch from virgin to mated behaviour in this species.     

Effects of the ecdysteroid agonists RH 5849 an RH 5992, alone and in combination with a juvenile hormone analogue, pyriproxyfen, on larvae ofSpodoptera exigua

Biological activity assays with RH 5849 and RH 5992 indicated that both compounds affected growth and development of last-instar larvae ofSpodoptera exigua (Hübner) (Lepidoptera: Noctuidae) in a dose-dependent manner. Within the first 24 h after treatment by continuously offering leaves dipped in a water solution of ≥50 mg/l RH 5849 and ≥0.5 mg/l RH 5992, symptoms of a prematurely induced larval moult and head capsule apolysis were visible. Intoxicated larvae died shortly afterwards, showing signs of unsuccessful ecdysis. LC₅₀-values of RH 5849 and RH 5992 for fifth-instarS. exigua larvae were 110 and 2.5 mg/l, respectively. Pyriproxyfen alone affected the larval stage and disturbed normal metamorphosis. One supernumerary larval instar occurred occasionally. LC₅₀-value for pyriproxyfen was 1.7 mg/l. Larvae simultaneously treated with RH 5849 or RH 5992 and pyriproxyfen, continued to grow until they attained a size and weight about 2–3 times that of the controls. This growth was accompanied by at least one and sometimes two supernumerary moults. Concerning thein vivo imaginal wing disc growth and development, only in larvae treated with 10 and 50 mg/l RH 5849 or 0.5 mg/l RH 5992, tracheole migration was observed earlier than in the controls. When applying 300 mg/l RH 5849 or 3–7 mg/l RH 5992, the discs remained small and no signs of tracheole migration were observed. In larvae simultaneously treated with RH 5849 or RH 5992 and pyriproxyfen, tracheole migration was not prematurely induced and a pupal cuticle was produced in the discs of larvae, undergoing a supernumerary moult. No clear signs of evagination were observed.     

Effects of a juvenile hormone analogue on the eggs, post-embryonic development, metamorphosis and diapause induction of the Colorado potato beetle, Leptinotarsa decemlineata

The effect of a juvenile hormone analogue, S-71639, was tested on the eggs, four larval instars and adults of the Colorado potato beetle, Leptinotarsa decemlineata Say, by topical application or after treatment of the foodplant. The last larval instar is very sensitive to S-71639. Treatment of this instar delayed the onset of pupation and prevented adult emergence. Treated animals showed severe abnormalities, but they were not immediately killed at the doses used in this study. Treatment of larvae also interfered with the photoperiodic induction of diapause. Adults, kept under diapausing conditions, started to lay eggs after treatment with S-71639. The ovicidal effect of the compound was rather weak. The implications for practical use of S-71639 in control of the Colorado potato beetle are being discussed.

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Résumé L'effet d'un analogue de l'hormone juvénile, S-71639, a été testé sur les oeufs, les quatre stades larvaires et les adultes du doryphore, Leptinotarsa decemlineata Say, par application topique ou après traitement de la plante-hôte. Le dernier stade larvaire est très sensible au S-71639. Le traitement de ce stade retarde le début de la métamorphose et empêche l'émergence adulte. Les animaux traités montrent de graves anomalies, mais ne sont pas immédiatement tués par les doses utilisées dans cette étude. Le traitement des larves perturbe aussi l'induction photopériodique de la diapause. Les adultes placés dans des conditions de diapause, commencent à pondre après traitement au S-71639. L'effet ovicide de la substance est plutôt faible. Les implications pour l'utilisation pratique du S-71639 dans la lutte contre le doryphore sont discutées.

     

Total body nitrogen and total body carbon as indicators of body protein and body lipids in the melon fly Bactrocera cucurbitae: Effects of methoprene, a juvenile hormone analogue, and of diet supplementation with hydrolyzed yeast

The application of methoprene, and providing access to diet including hydrolyzed yeast, are treatments known to enhance mating success in the male melon fly Bactrocera cucurbitae Coquillett (Diptera: Tephritidae), supporting their use in mass rearing protocols for sterile males in the context of sterile insect technique (SIT) programmes. The objective of the present laboratory study was to investigate the effect of methoprene application and diet supplementation with hydrolyzed yeast (protein) on the turnover of body lipids and protein to confirm the feasibility of their application in melon fly SIT mass-rearing programmes. While females had access to a diet that included hydrolyzed yeast (protein), males were exposed to one of the following treatments: (1) topical application of methoprene and access to diet including protein (M+P+); (2) only diet including protein (M−P+); (3) only methoprene (M+P−) and (4) untreated, only sugar-fed, control males (M−P−). Total body carbon (TBC) and total body nitrogen (TBN) of flies were measured at regular intervals from emergence to 35 days of age for each of the different treatments. Nitrogen assimilation and turnover in the flies were measured using stable isotope (¹⁵N) dilution techniques. Hydrolyzed yeast incorporation into the diet significantly increased male body weight, TBC and TBN as compared to sugar-fed males. Females had significantly higher body weight, TBC and TBN as compared to all males. TBC and TBN showed age-dependent changes, increasing until the age of sexual maturity and decreasing afterwards in both sexes. Methoprene treatment did not significantly affect TBC or TBN. The progressive increase with age of TBC suggests that lipogenesis occurs in adult male B. cucurbitae, as is the case in other tephritids. Stable isotope dilution was shown to be an effective method for determining N uptake in B. cucurbitae. This technique was used to show that sugar-fed males rely solely on larval N reserves and that the N uptake rate in males with access to diet including hydrolyzed yeast was higher shortly after emergence and then stabilized. The implications of the results for SIT applications are discussed.     

Effects of decapitation and ovariectomy on the regulation of juvenile hormone synthesis in the cockroach, Diploptera punctata

Corpora allata from Diploptera punctata females at adult ecdysis or at the end of the last-larval stadium, when implanted into decapitated females, underwent a cycle of juvenile hormone synthesis similar in timing and magnitude to that of glands implanted into control animals which had been starved and allatectomized. Starvation did not alter the cycle in rates of juvenile hormone synthesis of sham-operated animals.Decapitation of ovariectomized animals resulted in no cycle in rates of juvenile hormone synthesis by implanted adult corpora allata; however, implantation of an ovary along with the corpora allata into decapitated, ovariectomized hosts resulted in a cycle of juvenile hormone synthesis. In control animals, which retained their heads but were starved and allatectomized as well as ovariectomized, the implanted corpora allata showed a cycle of juvenile hormone synthesis only when implanted with an ovary. The maximal rates of juvenile hormone synthesis by the corpora allata in both experimental and control conditions were lower than normal, likely due to the repeated trauma of surgery. However, at no time from eclosion to the end of the first gonotrophic period was the brain necessary for the cyclic response of the corpora allata to the presence of the ovary.     

Potential use of tight junction modulators to reversibly open membranous barriers and improve drug delivery

The epithelial and endothelial barriers of the human body are major obstacles for drug delivery to the systemic circulation and to organs with unique environment and homeostasis, like the central nervous system. Several transport routes exist in these barriers, which potentially can be exploited for enhancing drug permeability. Beside the transcellular pathways via transporters, adsorptive and receptor-mediated transcytosis, the paracellular flux for cells and molecules is very limited. While lipophilic molecules can diffuse across the cellular plasma membranes, the junctional complexes restrict or completely block the free passage of hydrophilic molecules through the paracellular clefts. Absorption or permeability enhancers developed in the last 40 years for modifying intercellular junctions and paracellular permeability have unspecific mode of action and the effective and toxic doses are very close. Recent advances in barrier research led to the discovery of an increasing number of integral membrane, adaptor, regulator and signalling proteins in tight and adherens junctions. New tight junction modulators are under development, which can directly target tight or adherens junction proteins, the signalling pathways regulating junctional function, or tight junction associated lipid raft microdomains. Modulators acting directly on tight junctions include peptides derived from zonula occludens toxin, or Clostridium perfringens enterotoxin, peptides selected by phage display that bind to integral membrane tight junction proteins, and lipid modulators. They can reversibly increase paracellular transport and drug delivery with less toxicity than previous absorption enhancers, and have a potential to be used as pharmaceutical excipients to improve drug delivery across epithelial barriers and the blood-brain barrier.     

Arylpropionic acid-derived NSAIDs: New insights on derivatization,anticancer activity and potential mechanism of action

NSAIDs displayed chemopreventive and anticancer effects against several types of cancers. Moreover, combination of NSAIDs with anticancer agents resulted in enhanced anticancer activity. These findings have attracted much attention of researchers working in this field. The 2-arylpropionic acid-derived NSAIDs represent one of the most widely used anti-inflammatory agents. Additionally, they displayed antiproliferative activities against different types of cancer cells. Large volume of research was performed to identify molecular targets responsible for this activity. However, the exact mechanism underlying the anticancer activity of profens is still unclear. In this review article, the anticancer potential, structure activity relationship and synthesis of selected profen derivatives were summarized. This review is focused also on non-COX targets which can mediate the anticancer activity of this derivatives. The data in this review highlighted profens as promising lead compounds in future research to develop potent and safe anticancer agents.